Ultrafast ¹H MAS NMR Crystallography for Natural Abundance Pharmaceutical Compounds

Magic angle spinning (MAS) NMR is a powerful method for the study of pharmaceutical compounds, and probes with spinning frequencies above 100 kHz enable an atomic-resolution analysis of sub-micromole quantities of fully protonated solids. Here, we present an ultrafast NMR crystallography approach for structural characterization of organic solids at MAS frequencies of 100-111 kHz. We assess the efficiency of ¹H-detected experiments in the solid state and demonstrate the utility of 2D and 3D homo- and heteronuclear correlation spectra for resonance assignments. These experiments are demonstrated for an amino acid, U-¹³C,¹⁵N-histidine, and also for the significantly larger, natural product Posaconazole, an antifungal compound investigated at natural abundance. Our results illustrate the power for characterizing organic molecules, enabled by exploiting the increased ¹H resolution and sensitivity at MAS frequencies above 100 kHz.